This research will examine the importance of biological and physical causes of variation in the production of bioactive secondary metabolites by tropical macroalgae and sponges. The research has important biomedical consequences because it will specifically search for marine natural products with tumor selectivity (in collaboration with Dr. Valeriote at the Josephine Ford Cancer Center, Detroit, MI), and it will focus on understanding what factors affect the yields of biomedically important marine natural products. First, differences in types and concentrations of secondary metabolites at different ages and life history stages, and among populations of selected seaweeds and sponges will be examined. Facultative changes in chemical defenses will be examined. Facultative changes in chemical defenses will be examined for seaweeds and sponges exposed to: 1) increasing grazing by herbivores and predators; and 2) different resource levels of light and nutrients. The proposed research will provide important on chemical variation and its causes and the ability and timing of seaweeds and sponges to change their allocation of chemical defenses.. The study will contribute to our limited knowledge of the chemical variability of seaweeds and marine invertebrates, the biological properties of marine natural products, and the relationship between natural adaptive functions of secondary metabolites and their biomedical potential. All extracts and isolated metabolites will be incorporated into an established testing program to determine their pharmacological activities in assays examining cytotoxicity (tumor selectivity). The pharmacological activities of seaweeds and sponges will be compared before and after experiments designed to induced changes in production of natural products.